PUPARIATION ACCELERATION IN FLESHFLY (SARCOPHAGA BULLATA) LARVAE BY THE PYROKININ/PBAN NEUROPEPTIDE FAMILY:STRUCTURE-ACTIVITY RELATIONSHIPS

Authors: Nachman, Ronald; ZDAREK, JAN - ACAD SCI CZECH REPUBLIC; Holman, G; HAYES, TIMOTHY - TEXAS A&M UNIVERSITY

Submitted to: Annals of the New York Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling such pests. The basic premise of this research is that peptides (short chains of amino acids) serve as internal messengers in insects to regulate vital functions. Peptides themselves are unsuitable for control measures due to their instability to insect digestive and degradative enzymes and environmental factors. New, selective control measures may be developed by designing chemicals that actively inhibit or stimulate peptide regulated functions, resulting in disruption of the internal environment of the insect. In this report, we explore the chemical and 3-dimensional shape requirements to trigger a developmental process known as "pupariation" in immature forms of a livestock pest, the fleshfly, by the "pyrokinin" class of insect peptides. We have delineated some of these requirements, and have identified several modifications which can confer activity greater than the naturally occurring peptides. The information will be useful in the development of mimics that are resistant to the processes insects normally use to inactivate peptides and, therefore, capable of disrupting this developmental process critical to the survival of livestock pests.

Technical Abstract: Members of the pyrokinin/PBAN insect neuropeptide family, which share the C-terminal pentapeptide sequence FXPRLa (X= G,S,T or V), accelerate pupariation in larvae of the fleshfly Sarcophaga bullata. The tetrapeptide sequence TPRLa represents the active core required to elicit a full pupariation acceleration response, and this sequence coincides with the four residues that comprise a type I Beta-turn adopted by the pyrokinins at the pupariation receptor site. The C-terminal residues R and L are the most critical for activity, as A replacement-analogs demonstrate little or no activity. Activity retention observed in an analog in which K replaces R suggests that a basic, positively charged species is required at this position. Two analogs blocked at the N- terminus demonstrate activity greater than a naturally occurring pyrokinin, probably as a result of resistance to aminopeptidase enzymes. An analog in which G replaces P induces not an acceleration but a delay in the onset of pupariation, raising the possibility that it may function as an anatagonist at the pupariation receptor site. These structure-activity studies suggest that uncharacterized natural pupariation factors in extracts of insect neural and neurohemal organs may contain the pyrokinin tetrapeptide sequence XPRLa (X-G,S,T,V or other residue).